Bronchial Asthma

Overview

Asthma = ↑tracheobronchial hyperresponsiveness → widespread spasmodic airway narrowing, reversible (spontaneous/therapy). Episodic: dyspnoea+cough+wheeze paroxysms. Severe unremitting = status asthmaticus (can be fatal). ~4% US population. ~50% onset <10yr. Adults: equal sexes; children: 2:1 M:F.

Etiopathogenesis — 2 types + mixed

Extrinsic (atopic/allergic) — commonest

Childhood/early adult onset. Strong personal/family allergy history (rhinitis, urticaria, eczema). Inhaled allergens (dust, pollen, danders, moulds); occupational asthma = variant. TRUE IgE-mediated Type I hypersensitivity — ↑serum IgE, +skin test. Two phases:

• Acute immediate — IgE-sensitised mast cells degranulate → histamine, leukotrienes, prostaglandins, PAF, eosinophil/neutrophil chemotactic factors → bronchoconstriction+oedema+mucus+cell accumulation
• Late phase — follows immediate, explains PROLONGED symptoms. More leucocyte mobilisation (basophils+more eosinophils/neutrophils) → more mediators, amplified effects. Injury also from neutrophils + eosinophil major basic protein (MBP)

Intrinsic (idiosyncratic/non-atopic)

Later adult onset. NEGATIVE personal/family history, negative skin test, NORMAL IgE. Triggered by viral URTI. Associated: nasal polyps, chronic bronchitis. No allergen identified usually; ~10% aspirin-hypersensitive (aspirin-sensitive asthma).

Mixed type

Many don’t fit cleanly. Early-onset = allergic component; late-onset = non-allergic. Either type: precipitated by cold/exercise/emotional stress.

Comparison

Morphology (similar in both types)

Gross: overdistended/overinflated lungs, bronchi/bronchioles occluded by viscid mucus plugs.

Micro: mucus plugs contain twisted epithelial strips = CURSCHMANN’S SPIRALS. Sputum: eosinophils + diamond-shaped CHARCOT-LEYDEN CRYSTALS (eosinophil-derived). Bronchial wall: ↑thickened basement membrane, submucosal oedema, infiltrate (lymphocytes/plasma cells/prominent eosinophils), hypertrophy of submucosal glands+smooth muscle. Bronchitis/emphysema changes may supervene, esp. INTRINSIC type.

Clinical features

Episodic — exacerbations + symptom-free periods. Paroxysms (minutes-hours). Continuous = status asthmaticus. Diagnosis: circulating eosinophilia + sputum spirals/crystals. Chronic → cor pulmonale.

Clinical relevance

Immediate+late phase structure explains why symptoms recur hours after allergen exposure ends, and why treatment needs both bronchodilators (immediate, mast-cell) AND anti-inflammatories (late, leucocyte-driven) — not one mechanism alone. Extrinsic vs intrinsic = LINKED discriminators, not independent facts — age/IgE/allergens all point same direction together, one predicts the others. Curschmann’s spirals + Charcot-Leyden crystals = specific findings directly reflecting pathophysiology (spirals from shed epithelium in thick mucus; crystals from eosinophil breakdown that late-phase specifically recruits). Intrinsic asthma’s cluster (nasal polyps+bronchitis+aspirin sensitivity) = recognisable together — aspirin-sensitive asthma should prompt suspicion for the whole intrinsic pattern, not just flag a drug allergy.

Overview

Asthma is a disease of increased tracheobronchial hyperresponsiveness to varied stimuli, producing widespread spasmodic airway narrowing that reverses spontaneously or with therapy. Clinically episodic — paroxysms of dyspnoea, cough, wheezing; a severe, unremitting form is status asthmaticus, which can be fatal. Common worldwide (~4% of the US population); occurs at all ages, but ~50% of cases begin before age 10. Adults: equal sex distribution; children: 2:1 male predominance.

Etiopathogenesis and Types

Two traditional etiologic types, plus a mixed pattern; the two main types have genuinely different immunologic mechanisms, not just different triggers.

1. Extrinsic (Atopic, Allergic) Asthma

The most common type; usually begins in childhood/early adult life. Strong personal/family history of allergic disease (rhinitis, urticaria, infantile eczema). Driven by hypersensitivity to inhaled allergens — house dust, pollens, animal danders, moulds; occupational asthma (fumes, gases, organic/chemical dusts) is a variant. This is a genuine IgE-mediated Type I hypersensitivity reaction (see Type I Hypersensitivity), with raised serum IgE and positive skin testing to the specific allergen, unfolding in two temporally distinct phases:

• Acute immediate response — IgE-sensitised mast cells on the mucosal surface degranulate, releasing histamine, leukotrienes, prostaglandins, platelet-activating factor, and eosinophil/neutrophil chemotactic factors. Net effect: bronchoconstriction, oedema, mucus hypersecretion, eosinophil/neutrophil accumulation.
• Late phase reaction — follows the immediate response and accounts for asthma’s prolonged manifestations. Driven by mobilisation of additional blood leucocytes (basophils, plus more eosinophils/neutrophils), releasing further mediators that amplify the same effects; inflammatory injury is compounded by neutrophils and by eosinophil-derived major basic protein (MBP).

2. Intrinsic (Idiosyncratic, Non-Atopic) Asthma

Develops later in adult life, with negative personal/family allergy history, negative skin test, and normal serum IgE. Typically triggered by a preceding viral upper respiratory tract infection. Commonly associated with nasal polyps and chronic bronchitis. No identifiable allergen in most cases, but ~10% become hypersensitive to drugs, most notably aspirin (aspirin-sensitive asthma).

3. Mixed Type

Many patients don’t cleanly fit either category. Early-onset disease tends to carry a strong allergic component; late-onset tends non-allergic. Either type can be precipitated by cold, exercise, or emotional stress.

Comparison

Morphology

Pathologic changes are similar in both major types (material typically from status asthmaticus autopsies, but expected similar in non-fatal disease).

Gross: overdistended, overinflated lungs; cut surface shows bronchi/bronchioles occluded by viscid mucus plugs.

Microscopy:

1. Mucus plugs contain twisted strips of normal/degenerated respiratory epithelium — Curschmann’s spirals.
2. Sputum shows numerous eosinophils and diamond-shaped eosinophil-derived crystals — Charcot-Leyden crystals.
3. Bronchial wall: thickened basement membrane of the epithelium, submucosal oedema, inflammatory infiltrate (lymphocytes, plasma cells, prominent eosinophils), hypertrophy of submucosal glands and bronchial smooth muscle.
4. Bronchitis/emphysema changes may supervene, especially in intrinsic asthma.

Clinical Features

Episodic — acute exacerbations interspersed with symptom-free intervals. Paroxysms of dyspnoea, cough, wheezing, typically lasting minutes to hours; continuous attacks constitute status asthmaticus. Diagnosis supported by circulating eosinophilia and sputum demonstration of Curschmann’s spirals/Charcot-Leyden crystals. Chronic cases may develop cor pulmonale.

Clinical Relevance

• The immediate-versus-late-phase structure of the Type I hypersensitivity reaction in extrinsic asthma explains a clinically important pattern: why symptoms can recur hours after allergen exposure ends, and why treatment must address both phases (bronchodilators for the immediate mast-cell-driven phase, anti-inflammatory therapy for the leucocyte-driven late phase) rather than a single mechanism alone.
• The extrinsic-versus-intrinsic contrast is best learned as a set of linked discriminators rather than independent facts — age of onset, IgE status, and the presence of allergens all point the same direction together, so recognising one strongly predicts the others.
• Curschmann’s spirals and Charcot-Leyden crystals are genuinely specific, testable morphologic findings that directly reflect the underlying pathophysiology — spirals from degenerated epithelium shed into thick mucus (a direct consequence of gland hypertrophy and mucus hypersecretion), crystals from breakdown of the eosinophils that the late-phase reaction specifically recruits.
• Intrinsic asthma’s association with nasal polyps, chronic bronchitis, and aspirin sensitivity is a clinically recognisable cluster worth learning together — encountering aspirin-sensitive asthma in a patient should prompt suspicion for the intrinsic pattern as a whole, not just flag a drug allergy in isolation.

• Type I hypersensitivity in extrinsic asthma: mast-cell immediate response feeding into the leucocyte-driven late phase
• Extrinsic vs intrinsic asthma: linked discriminators compared side by side

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